The primary goals of the proposed training program are first to recruit talented and highly-motivated graduate students and second to provide them with first-rate training that will prepare them for careers in academic research as competitive, independent investigators. The program faculty's research interests span a wide range of questions regarding host-microbe interactions and related topics in pathogenesis, which allows the entering trainee a considerable breadth of choice of experimental systems, approaches, and research topics. Training options include animal and human systems, thus enhancing our ability to attract and train Ph.D. and M.D./Ph.D. students for research careers. Another strength of the proposed training grant is the quality of the research programs of the participating faculty. This proposal includes 19 well-funded program faculty members who have productive, timely, and energetic research efforts in numerous areas of current interest. Particular areas of strength are molecular genetics of bacterial, parasitic, and viral pathogenesis; cellular and immunobiology of parasites; B cell activation and interaction with T helper cells and lymphokines; mucosal immune responses; signaling events in host-pathogen interactions; involvement of various immune mechanisms in resistance to infectious diseases including those caused by bacteria, fungi, parasites and retroviruses such as HIV and mouse AIDS (MAIDS) virus; immunotherapeutics and vaccine design. These areas are pursued using the full range of modern genetic, immunblogic, biochemical, and molecular biologic techniques. We have outstanding facilities and resources to facilitate the application of these techniques, including new or renovated laboratories. The proposal also benefits from the presence of strong existing graduate programs leading to the Ph.D. degree. Training in molecular pathogenesis spans six departments that encompass two graduate programs - Molecular and Cellular Biology and Program in Experimental and Molecular Medicine - with the former containing the majority of the participating faculty and students. Consistent with this organization, graduate training in molecular pathogenesis at Dartmouth is an interdisciplinary approach that is nurtured by a highly interactive environment in which the trainees are regularly exposed to diverse areas of faculty expertise, from clinical to basic science studies, in a variety of forums, including a number of advanced courses, weekly seminar series and journal clubs, and retreats.